Brown adipose tissue (BAT or brown fat) is a thermogenic organ that plays a critical role in non- shivering thermogenesis with the purpose of generating heat in response to cold stress. Beginning in the 1980s, it was suggested that BAT thermogenesis might be an important therapeutic avenue for the treatment of obesity, and the role of BAT in energy balance has been studied extensively in both rodents and humans. Unfortunately, whether BAT thermogenesis plays a role in body weight regulation apart from its thermoregulatory function, is controversial until today. It is well known that most mammals, including humans, have abundant BAT during the perinatal period, however prominent depots disappear shortly after the perinatal period and it has been widely assumed the same was true for humans. Recently, numerous papers have appeared in the positron emission tomography (PET) literature identifying symmetric foci of intense uptake of 18F-deoxy-D-glucose (FDG) uptake in humans, and correlative CT clearly indicates that these sites are adipose tissue. Moreover, the magnitude of uptake showed hallmarks of functional BAT, including augmentation by cold stress and reduction by nonselective beta adrenergic blockers. Indeed, very recent PET literature has unequivocally demonstrated the existence of functional BAT in humans, strongly suggesting that most, if not all, humans have some functional BAT. However, it is unclear whether uptake of FDG in BAT represents an increase in oxidative metabolism (i.e. thermogenesis) and, if so, whether BAT oxidative metabolism contributes to the overall metabolic rate of young adults. This proposal will determine, using dynamic oxygen-15 (O15) positron emission tomography (PET), whether BAT thermogenesis can be activated in adults during cold stress and will establish the relationship between actual BAT thermogenesis and uptake of F18-deoxy-D-glucose (FDG), a widely used (but indirect) measure of BAT metabolism. Finally, as routine monitoring of BAT thermogenesis will require low-cost technologies other than PET imaging, we propose to test and validate near- infrared spectroscopy (NIRS) as an indirect measure of BAT oxygen consumption by correlating changes in regional O2 saturation, measured by NIRS, with direct measures of oxygen metabolism in BAT, measured by O15 PET. This study will establish the magnitude of BAT thermogenesis in individuals, and may provide a simple and cost-effective means of monitoring BAT thermogeneis in man. A better understanding of BAT thermogenesis might possibly lead to more effective approaches to weight control in obese subjects. ) PUBLIC HEALTH RELEVANCE: The relevance of this proposal for public health is the potential for improved weight control in obese subjects. Moreover, these studies will provide important physiological information about fat metabolism that will likely translate into novel pharmacological approaches for the treatment of obesity.